Intra-and interobserver reliability of ocular surface analyzer LacryDiag

AIM:To invastigate intra-and interobserver reliability of interferometry,tear meniscus height(TMH)measurement and meibography(MBG)of an ocular surface analyzer,LacryDiag(Quantel Medical,France).METHODS:Five consecutive measurements and subsequent analysis of interferometry,TMH,and MBG were recorded by two examiners using the LacryDiag.To assess intra-and interobserver reliability,we used Cohen’s kappa for categorical variables(interferometry),or intraclass correlation coefficient for continuous variables(TMH,MBG).RESULTS:Thirty eyes of 30 examinees were included.For both observers,there was excellent intraobserver reliability for MBG(0.955 and 0.970 for observer 1 and 2,respectively).Intraobserver reliability for observer 1 was substantial for interferometry(0.799),and excellent for TMH(0.863).Reliability for observer 2 was moderate for interferometry(0.535)and fair to good for TMH(0.431).Interobserver reliability was poor for interferometry(0.074)and fair to good for TMH(0.680)and MBG(0.414).CONCLUSION:LacryDiag ocular surface analyzer in our study proves to be a reliable noninvasive tool for the evaluation of TMH and MBG.As for interferometry,poor interobserver reliability,fair to good intraobserver reliability for observer 1,and moderate for observer 2,leave room for improvement.

Prevalence of posttraumatic stress disorder following acute coronary syndrome and clinical characteristics of patients referred to cardiac rehabilitation

BACKGROUND Studies have demonstrated that patients who have experienced acute coronary syndrome(ACS)have an increased risk of developing posttraumatic stress disorder(PTSD)and experiencing worse survival outcomes than those who do not develop PTSD.Nevertheless,the prevalence rates of PTSD following ACS vary widely across studies,and it is noteworthy that in most cases,the diagnosis of PTSD was based on self-report symptom questionnaires,rather than being established by psychiatrists.Additionally,the individual characteristics of patients who develop PTSD after ACS can differ widely,making it difficult to identify any consistent patterns or predictors of the disorder.AIM To investigate the prevalence of PTSD among a large sample of patients undergoing cardiac rehabilitation(CR)after ACS,as well as their characteristics in comparison to a control group.METHODS The participants of this study are patients who have experienced ACS with or without undergoing percutaneous coronary intervention and are enrolled in a 3-wk CR program at the largest CR center in Croatia,the Special Hospital for Medical Rehabilitation Krapinske Toplice.Patient recruitment for the study took place over the course of one year,from January 1,2022,to December 31,2022,with a total of 504 participants.The expected average follow-up period for patients included in the study is about 18 mo,and currently ongoing.Using self-assessment questionnaire for PTSD criteria and clinical psychiatric interview,a group of patients with a PTSD diagnosis was identified.From the participants who do not have a PTSD diagnosis,patients who would match those with a PTSD diagnosis in terms of relevant clinical and medical stratification variables and during the same rehabilitation period were selected to enable comparability of the two groups.RESULTS A total of 507 patients who were enrolled in the CR program were approached to participate in the study.Three patients declined to participate in the study.The screening PTSD Checklist-Civilian Version questionnaire was completed by 504 patients.Out of the total sample of 504 patients,74.2%were men(n=374)and 25.8%were women(n=130).The mean age of all participants was 56.7 years(55.8 for men and 59.1 for women).Among the 504 participants who completed the screening questionnaire,80 met the cutoff criteria for the PTSD and qualified for further evaluation(15.9%).All 80 patients agreed to a psychiatric interview.Among them,51 patients(10.1%)were diagnosed with clinical PTSD by a psychiatrist according to Diagnostic and Statistical Manual of Mental Disorders criteria.Among the variables analyzed,there was a noticeable difference in the percentage of theoretical maximum achieved on exercise testing between the PTSD and non-PTSD groups.Non-PTSD group achieved a significantly higher percentage of their maximum compared to the PTSD group(P=0.035).CONCLUSION The preliminary results of the study indicate that a significant proportion of patients with PTSD induced by ACS are not receiving adequate treatment.Furthermore,the data suggest that these patients may exhibit reduced physical activity levels,which could be one of the possible underlying mechanisms in observed poor cardiovascular outcomes in this population.Identifying cardiac biomarkers is crucial for identifying patients at risk of developing PTSD and may derive benefits from personalized interventions based on the principles of precision medicine in multidisciplinary CR programs.

Quo vadis cardiac rehabilitation;the role of comprehensive cardiac rehabilitation in modern cardiology

In accordance with the guidelines established by prominent European and global cardiology associations,comprehensive cardiac rehabilitation(CR)stands as an officially endorsed and highly recommended therapeutic approach(class I recommendations;level of evidence A)for a diverse spectrum of cardiac patients.Nevertheless,it is a cause for concern to observe that fewer than 50%of eligible patients are being effectively referred for CR,whether in an outpatient or in-patient setting.Concurrently,studies reveal that a substantial proportion of individuals with atherosclerotic cardiovascular disease maintain unhealthy lifestyles and exhibit suboptimal management of modifiable cardiovascular risk factors,including hypertension,lipid levels,and diabetes.Beyond the conven-tional patient profile encompassing those recovering from acute coronary syndrome with or without percutaneous coronary intervention,as well as patients who have undergone coronary or valvular surgery,contemporary CR now emphasizes specialized subgroups of patients.These include frail elderly patients,the female population with its unique considerations,individuals burdened by multiple cardiovascular comorbidities,those who have developed psychological consequences due to a cardiac illness and particularly those grappling with chronic heart failure.This editorial seeks to offer a state-of-the-art assessment of the significance and role of comprehensive CR within modern cardiology.

Spontaneous gastric hematoma as a rare cause of acute abdomen:A case report

BACKGROUND Spontaneous gastric hematoma is an exceedingly rare condition characterized by the accumulation of blood within the gastric wall without any apparent iatrogenic or traumatic cause.Coagulopathies are the most frequent cause of gastric he-matomas.However,other causes include amyloidosis,pancreatitis,visceral vas-cular aneurysms,endoscopy complications and others.The pathophysiology of spontaneous gastric hematoma is not completely understood.However,it is postulated that it is caused by disruption of submucosal vessels that leads to dissection of the muscularis layer and formation of false lumen.The rarity of this condition increases the challenge of diagnosis,and there is no standard treatment protocol.CASE SUMMARY We present the case of a spontaneous gastric hematoma in a 22-year-old male.He presented to our emergency department complaining of pain in the left flank area lasting for 2 wk.There was no history of trauma,antico-agulant medications or endoscopy procedures.His hemoglobin and hematocrit levels were slightly lower than normal.Multi-slice computed tomography,ultrasound and endoscopy confirmed a gastric intramural hematoma.We recommended conservative treatment because there was no hemodynamic instability nor significant bleeding.The patient responded well,and there were no unexpected events.At the 3-mo follow-up,the ultrasound exa-mination revealed complete regression of the hematoma.CONCLUSION After reviewing the literature and our experience,we recommend that more of these cases should be treated conservatively.The tendency to treat these cases with potentially burdensome procedures such as total or subtotal gastrectomy should be significantly reduced.

Current concept in the diagnosis,treatment and rehabilitation of patients with congestive heart failure

Heart failure(HF)is a major public health problem with a prevalence of 1%-2%in developed countries.The underlying pathophysiology of HF is complex and as a clinical syndrome is characterized by various symptoms and signs.HF is classified according to left ventricular ejection fraction(LVEF)and falls into three groups:LVEF≥50%-HF with preserved ejection fraction(HFpEF),LVEF<40%-HF with reduced ejection fraction(HFrEF),LVEF 40%-49%-HF with mid-range ejection fraction.Diagnosing HF is primarily a clinical approach and it is based on anamnesis,physical examination,echocardiogram,radiological findings of the heart and lungs and laboratory tests,including a specific markers of HF-brain natriuretic peptide or N-terminal pro-B-type natriuretic peptide as well as other diagnostic tests in order to elucidate possible etiologies.Updated diagnostic algorithms for HFpEF have been recommended(H2FPEF,HFA-PEFF).New therapeutic options improve clinical outcomes as well as functional status in patients with HFrEF(e.g.,sodium-glucose cotransporter-2-SGLT2 inhibitors)and such progress in treatment of HFrEF patients resulted in new working definition of the term“HF with recovered left ventricular ejection fraction”.In line with rapid development of HF treatment,cardiac rehabilitation becomes an increasingly important part of overall approach to patients with chronic HF for it has been proven that exercise training can relieve symptoms,improve exercise capacity and quality of life as well as reduce disability and hospitalization rates.We gave an overview of latest insights in HF diagnosis and treatment with special emphasize on the important role of cardiac rehabilitation in such patients.

Effect of COVID-19 on management of type 1 diabetes:Pushing the boundaries of telemedical healthcare

The new coronavirus disease 2019(COVID-19)pandemic posed a great burden on health care systems worldwide and is an enormous and real obstacle in providing needed health care to patients with chronic diseases such as diabetes.Parallel to COVID-19,there have been great advances in technology used for management of type 1 diabetes,primarily insulin pumps,sensors,integrated and closed loop systems,ambulatory glucose profile software,and smart phone apps providing necessary essentials for telemedicine implementation right at the beginning of the COVID-19 pandemic.The results of these remote interventions are reassuring in terms of glycemic management and hemoglobin A1c reductions.However,data on long-term outcomes and cost reductions are missing as well as proper technical infrastructure and government health policy support.

Quadricuspid aortic valve and right ventricular type of myocardial bridging in an asymptomatic middle-aged woman:A case report

BACKGROUND Quadricuspid aortic valve(QAV)is a very rare congenital cardiac defect with the incidence of 0.0125%-0.033%(<0.05%)predominantly causing aortic regurgitation.A certain number of patients(nearly one-half)have abnormal function and often require surgery,commonly in their fifth or sixth decade.QAV usually appears as an isolated anomaly but may also be associated with other cardiac congenital defects.Echocardiography is considered the main diagnostic method although more and more importance is given to computed tomography(CT)and magnetic resonance imaging(MRI)as complementary methods.CASE SUMMARY A 60-year-old female patient was referred for transthoracic ultrasound of the heart as part of a routine examination in the treatment of arterial hypertension.She did not have any significant symptoms.QAV was confirmed and there were no elements of valve stenosis with moderate aortic regurgitation.At first,it seemed that in the projection of the presumed left coronary cusp,there were two smaller and equally large cusps along with two larger and normally developed cusps.Cardiac CT imaging was performed to obtain an even more precise valve morphology and it showed that the location of the supernumerary cusp is between the right and left coronary cusp,with visible central malcoaptation of the cusps.Also,coronary computed angiography confirmed the right-type of myocardial bridging at the distal segment of the left anterior descending coronary artery.Significant valve dysfunction often occurs in middle-aged patients and results in surgical treatment,therefore,a 1-year transthoracic echocardiogram control examination and follow-up was recommended to our patient.CONCLUSION This case highlights the importance of diagnosing QAV since it leads to progressive valve dysfunction and can be associated with other congenital heart defects which is important to detect,emphasizing the role of cardiac CT and MRI.

A non-contiguous recurrence of the ciliary body melanoma—is cataract surgery a risk factor?

Dear Editor,We would like to present a case of non-contiguous recurrence of ciliary body melanoma following cataract surgery, detected by ultrasound biomicroscopy(UBM), three years after ruthenium-106(106 Ru) brachytherapy.Ultrasound biomicrosopy is a crucial tool in analysis of localization, size, and borders of the ciliary body tumours, local invasion, and follow-up after treatment[1]. According to the guidelines[2], examination of treated eyes should be performed every 3-6 mo following brachytherapy, actively searching for complications or tumour recurrence.

Euglycemic diabetic ketoacidosis:A rare but serious side effect of sodium-glucose co-transporter 2 inhibitors

Sodium-glucose co-transporter 2(SGLT2)inhibitors are an insulin-independent class of oral antihyperglycemic medication and from recently established therapy in chronic heart failure patients.A rare,but potentially life-threatening complication of SGLT2 inhibitor use is euglycemic diabetic ketoacidosis.We described a case of a middle-aged male patient with type 2 diabetes who developed metabolic ketoacidosis after a few days of empagliflozin administration.SGLT2 inhibitor related ketoacidosis presents with euglycemia or only modestly elevated glucose blood concentrations,which causes delayed detection and treatment of ketoacidosis.There are multiple possible risk factors and mechanism that might contribute to the pathogenesis of ketoacidosis.It is implied that SGLT2 inhibitor use and prescription by non-diabetologists(cardiologists,nephrologists,family physicians,etc.)will continue to grow in the future.It is important to inform the general cardiac public about this rare but serious side effect of SGLT2 inhibitors.

Bicuspid aortic valve with associated aortopathy, significant left ventricular hypertrophy or concomitant hypertrophic cardiomyopathy: A diagnostic and therapeutic challenge

Due to its prevalence of 0.5%to 2%in the general population,with a 75%predominance among men,bicuspid aortic valve is the most common congenital heart defect.It is frequently accompanied by other cardiac congenital anomalies,and clinical presentation can vary significantly,with stenosis being the most common manifestation,often resulting in mild to moderate concentric hypertrophy of the left ventricle.Echocardiography is the primary diagnostic modality utilized for establishing the diagnosis,and it is often the sole diagnostic tool relied upon by clinicians.However,due to the heterogeneous clinical presentation and possible associated anomalies(which are often overlooked in clinical practice),it is necessary to employ various diagnostic methods and persist in finding the accurate diagnosis if multiple inconsistencies exist.By employing this approach,we can effectively manage these patients and provide them with appropriate treatment.Through a clinical case from our practice,we provide an overview of the literature on bicuspid aortic valve with aortophaty and the possible association with hypertrophic cardiomyopathy,diagnostic methods,and treatment options.This review article highlights the critical significance of achieving an accurate diagnosis in patients with bicuspid aortic valve and significant left ventricular hypertrophy.It is crucial to exclude other possible causes of left ventricular outflow tract obstruction,such as sub-or supra-aortic obstructions,and hypertrophic cardiomyopathy.

Gastric pentadecapeptide BPC 157 in cytoprotection to resolve major vessel occlusion disturbances,ischemia-reperfusion injury following Pringle maneuver,and Budd-Chiari syndrome

The stable gastric pentadecapeptide BPC 157 counteracts various venous occlusion-induced syndromes.Summarized are all these arguments,in the Robert’s cytoprotection concept terms,to substantiate the resolution of different major vessel occlusion disturbances,in particular ischemia-reperfusion injury following the Pringle maneuver and Budd-Chiari syndrome,which was obtained by BPC 157 therapy.Conceptually,there is new point(bypassed occluded or ruptured vessel,the equation endothelium maintenance→epithelium maintenance=blood vessel recruitment and activation towards defect or bypassing vessel occlusion),the recruitment of collateral blood vessels to compensate for vessel occlusion and reestablish blood flow.In this paper,we summarize the evidence of the native cytoprotective gastric pentadecapeptide BPC 157,which is stable in the human gastric juice,is a membrane stabilizer and counteracts gut-leaky syndrome.As a particular target,it is distinctive from the standard peptide growth factors,with particular molecular pathways involved,controlling VEGF and NO pathways.In the early 1990s,BPC 157 appeared as a late outbreak of the Robert’s and Szabo’s cytoprotection-organoprotection concept,epithelium,endothelium protection as previous theoretical/practical breakthrough in the 1980s,and brain-gut axis and gut-brain axis.As the time went on,with its reported effects,it is likely most useful theory practical implementation and justification.Meantime,several reviews suggest that BPC 157,which does not have a lethal dose(LD1),has profound cytoprotective activity,used to be demonstrated in ulcerative colitis and invented to multiple sclerosis trials.Likely,it may bring the theory to practical application,starting with the initial argument,no degradation in human gastric juice for more than 24 h,and thereby,the therapeutic effectiveness(including therapeutic per-oral regimen)and pleiotropic beneficial effects.

Anabolic androgenic steroid-induced liver injury:An update

Anabolic androgenic steroids(AASs)are a group of molecules including endogenous testosterone and synthetic derivatives that have both androgenic and anabolic effects.These properties make them therapeutically beneficial in medical conditions such as hypogonadism.However,they are commonly bought illegally and misused for their anabolic,skeletal muscle building,and performanceenhancing effects.Supraphysiologic and long-term use of AASs affects all organs,leading to cardiovascular,neurological,endocrine,gastrointestinal,renal,and hematologic disorders.Hepatotoxicity is one of the major concerns regarding AASs treatment and abuse.Testosterone and its derivatives have been most often shown to induce a specific form of cholestasis,peliosis hepatis,and hepatic benign and malignant tumors.It is currently believed that mechanisms of pathogenesis of these disorders include disturbance of antioxidative factors,upregulation of bile acid synthesis,and induction of hepatocyte hyperplasia.Most toxicity cases are treated with supportive measures and liver function normalizes with discontinuation of AAS.However,some long-term consequences are irreversible.AAS-induced liver injury should be taken in consideration in patients with liver disorders,especially with the increasing unintentional ingestion of supplements containing AAS.In this paper,we review the most current knowledge about AAS-associated adverse effects on the liver,and their clinical presentations,prevalence,and pathophysiological mechanisms.

Mechanisms of Hepatic Cholestatic Drug Injury

Drug-induced cholestasis represents a form of drug-induced liver disease that can lead to severe impairment of liver function.Numerous drugs have been shown to cause cholestasis and consequently bile duct toxicity.However,there is still lack of therapeutic tools that can prevent progression to advanced stages of liver injury.This review focuses on the various pathological mechanisms by which drugs expresstheir hepatotoxic effects,as well as consequences of increased bile acid and toxin accumulation in the hepatocytes.

An Update on Efficacy and Safety of Emerging Hepatic Antifibrotic Agents

Liver fibrosis represents a response to chronic liver injury.Metabolic dysfunction-associated fatty liver disease and metabolic dysfunction-associated steatohepatitis are the most common chronic liver diseases,both with increasing incidence.Therefore,there is a great impetus for development of agents targeting these conditions.Accumulating data on possible treatment options for liver fibrosis are emerging in the literature.However,despite extensive research and much effort in the field,approved agents for liver fibrosis are still lacking.In this critical review,we have summarized the main data about specific treatment options for liver fibrosis gained from ongoing clinical trials,with an emphasis on efficacy and safety of these agents.

Therapeutic Perspectives of IL1 Family Members in Liver Diseases:An Update

Interleukin(IL)1 superfamily members are a cornerstone of a variety of inflammatory processes occurring in various organs including the liver.Progression of acute and chronic liver diseases regardless of etiology depends on the stage of hepatocyte damage,the release of inflammatory cytokines and disturbances in gut microbiota.IL1 cytokines and re-ceptors can have pro-or anti-inflammatory roles,even dual functionalities conditioned by the microenvironment.Devel-oping novel therapeutic strategies to block the IL1/IL1R sign-aling pathways seems like a reasonable option.This mode of action is now exploited by anakinra and canakinumab,which are used to treat different inflammatory illnesses,and studies in liver diseases are on the way.In this mini review,we have focused on the IL1 superfamily members,given their cru-cial role in liver inflammation diseases,specifically discussing their potential role in developing new treatment strategies.

Obesity Paradox in Chronic Liver Diseases:Product of Bias or a Real Thing?

In recent years,evidence supporting the theory of obesity paradox has increased,showing that obese/overweight people with prevalent chronic diseases experience lower mortality compared with patients of normal weight.So far,evidence is most comprehensive in cardiovascular and chronic renal diseases;however,published studies are prone to many biases,enabling us to reach a definite conclusion.Available data in chronic liver disease is scarce and ambiguous.Obesity is traditionally associated with nonalcoholic fatty liver disease and steatosis in viral hepatitis and as such one would not expect the obesity paradox to be a real possibility in liver disease.Yet,there seem to be new data indicating the opposite-the obesity paradox exists in severe and end-stage liver cirrhosis,which could be attributed to a better lean mass in patients with higher body mass index,meaning that sarcopenia,as one of the most important prognostic factors of survival,is less likely to be present.Nonetheless,the problem of various methodological problems addressing the association between body weight and mortality,which is present both in liver disease and other chronic diseases,are preventing us from attaining an unanimous conclusion.Still,we should be aware that the obesity paradox might be true,especially in severe and end-stage illness.This suggests focusing our efforts toward preserving or building up fat-free mass and decreasing infiammatory activity responsible for catabolism and sarcopenia,and implying that the underlaying cause should be treated.

Update on the Development of Anti-Viral Agents Against Hepatitis C

Hepatitis C virus (HCV) infects nearly 170 million people worldwide and causes chronic hepatitis, cirrhosis, and hepatocellular carcinoma. The search for a drug regimen that maximizes efficacy and minimizes side effects is quickly evolving. This review will discuss a wide range of drug targets currently in all phases of development for the treatment of HCV. Direct data from agents in phase Ⅲ/Ⅳ clinical trials will be presented, along with reported side-effect profiles. The mechanism of action of all treatments and resistance issues are highlighted. Special attention is given to available trial data supporting interferon-free treatment regimens. HCV has become an increasingly important public health concern, and it is important for physicians to stay up to date on the rapidly growing novel therapeutic options.

Noninvasive Fibrosis Assessment in Chronic Hepatitis C Infection: An Update

Liver biopsy is historically the gold standard for liver fibrosis assessment of chronic hepatitis C patients.However,with the introduction and validation of noninvasive tests(NITs)to evaluate advanced fibrosis,and the direct-acting antiviral agents for treatment of chronic hepatitis C virus(HCV),the role of NITs have become even more complex.There is now need for longitudinal monitoring and elucidation of cutoff values for prediction of liver-related complication after sustained virological response.The aim of this report is to provide a critical overview of the various NITs available for the assessment of liver fibrosis in HCV patients.

Targeting the Wnt Signaling Pathway in Liver Fibrosis for Drug Options:An Update

morbidity and mortality for healthcare systems worldwide.It imparts an enormous economic burden to societies,making continuous research and informational updates about its pathogenesis and treatment crucial.This review′s focus is on the current knowledge about the Wnt signaling path-way,serving as an important pathway in liver fibrosis development and activation of hepatic stellate cells(HSCs).Two types of Wnt pathways are distinguished,namely the ß-catenin-dependent canonical and non-canonical Ca^(2+) or planar cell polarity(PCP)-dependent pathway.The dynamic balance of physiologically healthy liver and hepatocytes is disturbed by repeated liver injuries.Activation of theß-catenin Wnt pathway prevents the regeneration of hepatocytes by the replacement of extracellular matrix(ECM),leading to the appearance of scar tissue and the formation of regenerated nodular hepatocytes,lacking the original function of healthy hepatocytes.Therefore,liver function is reduced due to the severely advanced disease.Selective inhibition ofß-catenin inhibits inflammatory processes(since chemokines and pro-inflammatory cytokines are produced during Wnt activation),reduces growth of activated HSCs and reduces collagen synthesis and angiogenesis,thereby reducing the progression of liver fibrosis in vivo.While the canonical Wnt pathway is usually inactive in a physiologically healthy liver,it shows activity during cell regeneration or renewal and in certain pathophysiological conditions,such as liver diseases and cancer.Targeted blocking of some of the basic components of the Wnt path-way is a therapeutic approach.These include the frizzled transmembrane receptor(Fz)receptors using the secreted frizzled-related protein family(sFRP),Fz-coreceptors low-density LRP 5/6 through dickkopf-related protein 1(DKK1)or niclosamide,glycogen kinase-3 beta(GSK-3β)using SB-216763,cyclic-AMP response element-binding protein(CBP)using PRI-724 and ICG-001,the lymphoid enhancer binding factor(LEF)/T cell-specific transcription factor(TCF)system as well as Wnt inhibitory factor 1(WIF1)and miR-17-5p using pinostilbene hydrate(PSH).Significant progress has been made in inhibiting Wnt and thus stopping the progression of liver fibrosis by diminishing key components for its action.Comprehending the role of the Wnt signaling pathway in liver fibrosis may lead to discovery of novel targets in liver fibrosis therapeutic strategies’development.

Hypothyroidism and Nonalcoholic Fatty Liver Disease:Pathophysiological Associations andTherapeutic Implications

Nonalcoholic fatty liver disease(NAFLD)is a complex clinical entity which can be secondary to many other diseases including hypothyroidism,characterized by lowering of thyroid hormones and increased thyroid stimulating hormone(TSH).A lot of emerging data published recently advocates the hypothesis that hypothyroid induced NAFLD could be a separate clinical entity,even suggesting possible treatment options for NAFLD involving substitution therapy for hypothyroidism along with lifestyle modifications.In addition,a whole new field of research is focused on thyromimetics in NAFLD/NASH treatment,currently in phase 3 clinical trials.In this critical review we summarized epidemiological and pathophysiological evidence linking these two clinical entities and described specific treatment options with the accent on promising new agents in NAFLD treatment,specifically thyroid hormone receptor(THR)agonist and its metabolites.